Project Summary/Abstract Early caregiving adversities (ECAs) alter the development of neuro-affective circuitry implicated in internalizing disorders, increasing risk for psychopathology later in life. Given that one quarter of children in the US experience ECAs, the identification of neurobehavioral targets for intervention is imperative. Persistence to setbacks is a crucial regulatory skill that a) is associated with reduced internalizing symptoms in adults, b) implicates adaptive neuro-affective circuit function, and c) is malleable during early development, making it a promising target for intervention following ECA exposure. The goal of the current proposal is to characterize the neural and behavioral mechanisms of persistence to setbacks in ECA-exposed youth and comparisons, and identify corresponding links to mental health outcomes. Approach: Using the Research Domain Criterion (RDoC) framework, we will investigate two neurobehavioral factors underlying persistence to setbacks: (a) effort based motivation, which implicates fronto-striatal circuitry and (b) regulatory responses to setbacks, which involves prefrontal-amygdala circuitry. We will conduct this study during middle childhood?a sensitive period of neuro-affective development?in order to identify factors associated with resilient mental health trajectories following ECAs. Participants will complete a child-friendly functional MRI task, where they will choose between hard-effort or easy-effort tasks and receive rewards or setbacks (50% probability), allowing us to examine effort choices and response to setbacks at the behavioral and neural level. Aim 1 of the proposed study will delineate group-level effects of ECA exposure on neurobehavioral phenotype of persistence to setbacks (i.e. effort choices and responses to setbacks). Aim 2 will identify individual-level associations between the neurobehavioral phenotype of persistence and resilience in ECA-exposed children. Specifically, we will investigate how neural and behavioral measures of effort-based motivation and regulatory responses to setbacks moderate the effects of ECA status on internalizing psychopathology. This analytic plan will allow for the identification of neurobehavioral factors associated with resilient mental health outcomes within the ECA- exposed group. These findings will elucidate the neural and behavioral mechanisms underlying persistence to setbacks in young children, and in turn, yield insight into how this adaptive coping skill may promote healthy emotional development following ECA exposure. This research has direct links to NIMH's Strategic Aims: by using multiple levels of analysis to investigate predictors of mental health outcomes in children with ECA histories, we can gain better traction in developing interventions for the treatment and prevention of mental illness in high-risk children.